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Biomedical subjects

O B Eden

Publications and source records attributed to O B Eden.

At least 73 records · Page 4Linked to original sources
PubMed1999

Paediatric oncology and intensive care treatments: changing trends.

OBJECTIVES: To review the outcome of patients with childhood malignancy requiring intensive care treatment and to assess whether there is any secular trend for improved outcome. DESIGN: Retrospective chart reviews of 74 consecutive admissions to a paediatric intensive care unit from a regional paediatric oncology centre between 1990 and 1997. During the same period there were 6419 admissions to the oncology unit, 814 of whom were new cases. RESULTS: The overall survival at discharge from the intensive care unit was 49 of 74. Patients with either systemic or respiratory infection requiring ventilation had the poorest survival (13 of 31) whereas postoperative patients had the best survival (15 of 15). However, patients with respiratory or systemic infection who required inotropic support with more than three agents all died compared with about one quarter of those needing no inotrope. All patients with systemic or respiratory infective illness were neutropenic and positive microbiological identification was possible in 13 of 21 and five of 18, respectively. Non-survivors had a higher mean acute physiology and chronic health evaluation system (APACHE-II) score than survivors (24.2 v 15.94, respectively) but no patient with a score of > 27 survived. CONCLUSION: Compared with previous series, there has been a great improvement in survival of oncology patients admitted to the intensive care unit especially those with either systemic or respiratory infection needing ventilation. Full intensive care treatment should be provided for these patients.

Adolescent↗
PubMed1998

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel.

UNLABELLED: During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. CONCLUSION: In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account.

Bone Marrow Transplantation↗
PubMed1998

Seasonal variations in the onset of childhood leukaemia and lymphoma.

Infection has long been suspected as a possible factor in the aetiology of leukaemia and lymphoma. If seasonal variation in the onset of disease could be shown in any of the diagnostic subgroups of leukaemia or lymphoma, this would provide supportive evidence of an aetiology linked to exposure to infection. All cases in the Manchester Children's Tumour Registry (aged 0-14 years at diagnosis) with acute lymphoblastic leukaemia (ALL), acute non-lymphocytic leukaemia (ANLL), Hodgkin's disease (HD) or non-Hodgkin lymphoma (NHL) between 1 January 1954 and 31 December 1996 were included in an analysis of seasonal variation in the month of first symptom and the month of diagnosis. Cases of common acute lymphoblastic leukaemia (c-ALL) diagnosed from 1979 onwards were also analysed separately. The groups considered for analysis were: all cases of ALL (n = 1070), ALL diagnosed between 18 and 95 months of age (n = 730), ALL diagnosed over 95 months of age (n = 266), c-ALL (n = 309), ANLL (n = 244), all infant acute leukaemias (ALL and ANLL under 18 months; n = 107), HD (n = 166) and NHL (n = 189). Using the Edwards method, both c-ALL and HD demonstrated significant seasonal variation (P = 0.037 and 0.001 respectively) in date of first symptom, with peaks occurring in November and December respectively. Using this method, no indication of seasonal variation was found in the other diagnostic groups for date of first symptom or in any of the diagnostic groups for date of diagnosis. For comparison with a previous study, a further analysis based on date of diagnosis for all ALL cases, using summer-winter ratios, showed a significant summer excess. These results provide supportive evidence for an infectious aetiology for c-ALL and HD, and possibly for all ALL, which warrants further investigation.

Adolescent↗
PubMed1998

Evidence that an HLA-DQA1-DQB1 haplotype influences susceptibility to childhood common acute lymphoblastic leukaemia in boys provides further support for an infection-related aetiology.

Comparison of DQA1 and DQB1 alleles in 60 children with common acute lymphoblastic leukaemia (c-ALL) and 78 newborn infant control subjects revealed that male but not female patients had a higher frequency of DQA1*0101/*0104 and DQB1*0501 than appropriate control subjects. The results suggest a male-associated susceptibility haplotype in c-ALL and supports an infectious aetiology.

Alleles↗
PubMed1998

Analysis of the immunophenotype of children treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia Trial XI (MRC UKALLXI). Medical Research Council Childhood Leukaemia Working Party.

Despite many years of meticulous immunophenotyping of childhood acute lymphoblastic leukaemia (ALL) cases the prognostic significance of some subtypes remains unclear. The Medical Research Council UKALLXI trial (1990-1996) in which uniform treatment has been given to 2090 children with ALL below the age of 18 years and above the age of 1 year, has afforded the opportunity to review these issues. Children with ALL of mature B cell type were not entered into this trial. Immunophenotype analysis was performed in each individual trial centre, but results were centrally reviewed in all cases, and were both available and considered adequate in 1934 (93%) of the first 2090 patients entered. The main diagnostic categories were early pre-B or null reported in 60 cases (3.1%), common ALL in 1242 (64.2%), pre-B in 252 (13.0%), 'common' or pre-B in 172 (8.9%) and T cell in 207 (10.7%) cases. Children with T cell disease were significantly more likely to be over the age of 10 years, with central nervous system disease at diagnosis and to be CD34 negative. They also had a higher incidence of high white cell count and were more likely to be of the French-American-British (FAB) L2 morphological subtype. Patients with 'null' cell disease tended to be less than 2 years or greater than 10 years of age, and CD13 and CD33 positive. CD10 was associated with lower white cell count (WBC) at diagnosis, younger age and FAB L1 morphological subtype. The presence of cytoplasmic immunoglobulin in pre-B cells was not associated with any specific clinical or laboratory features. CD34 positivity was less common in T cell patients and was associated with low WBC. Disease-free survival (DFS) and 95% confidence intervals (CI) at 5 years from diagnosis was 52% (95% CI: 44-59%) for T cell disease, 58% (95% CI: 43-73%) for early pre-B (or null cell) disease and 65% (95% CI: 62-68%) for common or pre-B disease; there being no significant difference between common and pre-B disease with regard to disease outcome. Patients with T cell disease had a worse prognosis than any other immunophenotype group (P < 0.00005). However this worse outcome was no longer significant after allowing for the other principal prognostic factors of age, gender and white cell count at diagnosis except for the very small number with WBC <20 x 10(9)/l and T cell disease. Those with CD10-positive leukaemia did better than those who were CD10 negative (P < 0.00005), with DFS at 5 years 64% (95% CI: 62-67%) for positive vs 56% (95% CI: 49-62%) for CD10 negative. CD10 positivity did not have independent significance when white count, gender and age were taken into account. CD13, CD33, and cytoplasmic mu positivity carried no prognostic significance.

Adolescent↗
PubMed1998

Lack of association between childhood common acute lymphoblastic leukaemia and an HLA-C locus dimorphism influencing the specificity of natural killer cells.

Previous serological studies documenting an association between acute lymphoblastic leukaemia (ALL) and HLA-Cw antigens suggested that the HLA-C locus might influence susceptibility to ALL. However, associations with more than one Cw antigen suggest that polymorphic variants shared by more than Cw allele could be involved. Recent studies have shown that the HLA-C locus encodes two ligands (NK1 and NK2) recognized by receptors on natural killer (NK) cells. HLA-Cw alleles encoding these ligands are dimorphic, dependent on whether they encode one or other NK ligand. To determine whether susceptibility to the common (CD10+) form of childhood ALL (c-ALL) is associated with NK1 or NK2, we carried out a molecular analysis of 94 childhood c-ALL patients and 136 infant controls. We found no difference in the frequency of NK1 and NK2 alleles, phenotypes or genotypes between the patients and controls, suggesting that this does not explain the role of the HLA-C locus in susceptibility to childhood c-ALL.

Female↗
PubMed1998

Growth hormone status in adults treated for acute lymphoblastic leukaemia in childhood.

OBJECTIVE: Growth hormone status was assessed in a cohort of 32 (16 male) adults who had received cranial irradiation (XRT) in childhood as part of their treatment for acute lymphoblastic leukaemia (ALL) and compared with 35 age matched young adults (18 male). DESIGN: Height and weight were measured in all subjects and the heights of the patients at XRT were obtained from their case notes. Each patient and control underwent two provocative tests of growth hormone (GH) secretion using insulin (0.2 IU/kg body weight) and arginine (20 g/m2). Basal serum insulin like growth factor-1 (IGF-1) and IGFBP-3 (binding protein-3) concentrations were also measured. RESULTS: The patient group had a significantly lower peak GH response to both provocative tests (P < 0.01), and lower IGF-1 and IGFBP-3 levels compared with the normal controls (P < 0.01). Nine of the patient group were severely GH deficient (peak GH response < 9 mU/l to both provocative agents) and a further 12 patients were GH insufficient (peak GH response < 20 mU/l to both tests with at least one peak GH response > 9 mU/l). Overall a significant median change in height from XRT to final height of -0.5 SDS was found which was even greater in the severely GH deficient group (median change in height of -2.1 SDS). CONCLUSION: These data suggest that a significant proportion of adults treated with cranial XRT in childhood with irradiation doses between 18-25 Gy, as part of their treatment for ALL, are severely GH deficient now and should be considered for GH replacement. Changes in GH secretion evolve with time following irradiation-induced damage to the hypothalamic-pituitary axis; therefore long-term surveillance will be required in those remaining patients, in whom GH status is considered currently to be insufficient or even normal.

Adolescent↗
PubMed1998

Spinal cord compression--do we miss it?

Four children with spinal cord compression due to malignant tumours are presented. The severity of the condition was not initially recognized by parents, or the nature of the likely cause by the initial physicians. Lower limb asymmetrical weakness, clear-cut sensory levels, and marked pain indicate need for urgent imaging and exclusion of a space occupying lesion. In 1997 diagnosis of Guillain-Barré syndrome should not be made without careful prior spinal imaging.

Child, Preschool↗
PubMed1998

Changes in protein turnover, IGF-I and IGF binding proteins in children with cancer.

Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1-13C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3-17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean +/- SEM: 250+/-28 and 228+/-22 microg l(-1), respectively). During FN, IGF-I fell to 156+/-22 microg l(-1) (p = 0.02), and rose to 276+/-27 microg l(-1) with recovery at 6 months (p = 0.004). Similarly, IGFBP-3 decreased from 4.0+/-0.2 mg l(-1) before chemotherapy to 3.0+/-0.3 mg l(-1) during FN (p = 0.01), and returned to 4.1+/-0.2 mg l(-1) at 6 months (p = 0.01). IGF-I correlated with IGFBP-3 (r = +0.7, p < 0.001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6+/-3.5 to 30.6+/-2.8 microg l(-1) (p = 0.004), whereas serum insulin decreased from 26.5+/-6.8 to 7.8+/-0.8 mU l(-1) (p = 0.03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3+/-0.6 to 6.7+/-0.8 mU l(-1) (p=0.01), and cortisol from 197+/-48 to 594+/-98 nmol l(-1) (p = 0.005). Albumin decreased from 47+/-2 to 38+/-2 g l(-1) (p = 0.004) and improved to 47+/-2 g l(-1) with recovery (p = 0.003). Protein synthesis increased from 4.5+/-0.4 to 5.0+/-0.6 g kg(-1)d(-1) before chemotherapy and during FN, while protein breakdown rose from 5.4+/-0.4 to 6.3+/-0.4 kg(-1)d(-1). Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress.

Adolescent↗
PubMed1998

Dental health in children with cancer.

This study investigated the dental health of children (aged 1-14 years) diagnosed with cancer 4-36 months earlier. Sixty patients were examined and interviewed; 43% had untreated decay and only 35% had seen a dentist since their malignancy had been diagnosed. A significant source of bacterial infection is not being treated in this at risk population. The level of dental disease and lack of dental prevention indicates a need to integrate medical and dental care.

Adolescent↗
PubMed1998

Costello syndrome: two cases with embryonal rhabdomyosarcoma.

Costello syndrome is a well delineated mental retardation syndrome of unknown aetiology in which the occurrence of benign tumours, especially papillomata, is recognised. We report two children in whom the diagnosis of Costello syndrome was made in the first months of life, who both developed a retroperitoneal embryonal rhabdomyosarcoma. Although not previously reported, the occurrence of this relatively uncommon childhood tumour in two girls with Costello syndrome suggests that an increased risk of malignancy may be part of this condition. The genetic basis of this susceptibility requires further clarification.

Child, Preschool↗
PubMed1998

Chemotherapeutic agents used in the treatment of childhood malignancies have direct effects on growth plate chondrocyte proliferation.

Short stature is one of the most well recorded long term sequelae for adult survivors of childhood malignancies. It has become increasingly apparent that cytotoxic chemotherapy, as well as craniospinal irradiation, has a major impact on growth, but there are virtually no studies which explore the mechanisms by which these cytotoxic drugs affect growth. We have used an in vitro system to investigate the direct effects of a range of chemotherapeutic agents on the proliferative responses of rat tibial growth plate chondrocytes, both in suspension and monolayer culture. The glucocorticoids and purine anti-metabolites reduced chondrocyte proliferation both in monolayer and suspension cultures and this resulted from an increase in cell doubling times with a concomittant reduction in the numbers of S phase cells. DNA damaging agents (e.g. actinomycin-D) were also able to reduce chondrocyte proliferation, both in monolayer and suspension culture. This, however, was the result of a cell cycle arrest and subsequent cell death. In our studies, methotrexate had no significant effect on the proliferative responses of the chondrocytes either in monolayer or suspension culture. These results indicate direct effects of a range of chemotherapeutic agents on the proliferative responses of growth plate chondrocytes. Both cytostatic and cytotoxic effects were observed although the impact of either the potential loss of cells from the proliferative pool during chondrocyte differentiation, or the reduction in the rate of chondrocyte turnover on long bone growth remains to be elucidated.

Animals↗
PubMed1997

Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.

Epidemiological evidence has suggested that some pediatric leukemias may be initiated in utero and, for some pairs of identical twins with concordant leukemia, this possibility has been strongly endorsed by molecular studies of clonality. Direct evidence for a prenatal origin can only be derived by prospective or retrospective detection of leukemia-specific molecular abnormalities in fetal or newborn samples. We report a PCR-based method that has been developed to scrutinize neonatal blood spots (Guthrie cards) for the presence of numerically infrequent leukemic cells at birth in individuals who subsequently developed leukemia. We demonstrate that unique or clonotypic MLL-AF4 genomic fusion sequences are present and detectable in neonatal blood spots from individuals who were diagnosed with acute lymphoblastic leukemia at ages 5 months to 2 years and, therefore, have arisen during fetal hematopoiesis in utero. This result provides unequivocal evidence for a prenatal initiation of acute leukemia in young patients. The method should be applicable to other fusion genes in children with common subtypes of leukemia and will be of value in attempts to unravel the natural history and etiology of this major subtype of pediatric cancer.

Artificial Gene Fusion↗
PubMed1997

The treatment of acute leukaemia.

Developments in supportive care, new regimens for induction of remission and consolidation therapy, and bone-marrow transplantation have improved the outlook for patients with acute leukaemia. The outlook, though, is influenced by age and factors related to the biology of the disease. In acute myeloid leukaemia age is such an important factor that it determines approach to therapy. Overcoming resistance to chemotherapy is an area that needs much attention.

Acute Disease↗